An estimated 600,000 individuals in the US suffer from cirrhosis and 14,000 of these patients are in end-stage disease and await liver transplant. Studies have suggested that up to 40-60% of cirrhosis patients have concomitant muscle wasting. The resultant frailty is a significant cause for functional decline, cirrhosis-related complications, hospitalizations, and mortality in patients with end-stage liver disease (ESLD). Liver transplant is the definitive cure for ESLD, but physical decline, independent of liver disease severity, is associated with increased risk of de-listing from transplant waitlists.
An estimated 40-50% of cirrhosis patients exhibit cirrhotic sarcopenia. Cirrhotic sarcopenia is a frequent complication in cirrhosis that adversely impacts the survival and quality of life of patients. Cirrhotic sarcopenia is a systemic disease resulting from hyperammonemia due to a dysfunctional urea cycle in cirrhosis, in which the muscle detoxifies the ammonia, but at the expense of muscle mass. Sarcopenia lowers the survival, decreases the chances of receiving a transplant, and increases the risks of cirrhosis-related complications in cirrhosis patients.
The current standard of care for patients with cirrhosis, such as patients with ESLD or cirrhotic sarcopenia, include lifestyle modifications, such as increased exercise and dietary interventions. Currently, there are no approved pharmacological interventions.
Given the lack of available therapies, there is still a need for agents, e.g., dietary compositions and therapeutics for treating liver diseases and disorders with hyperammonemia or muscle wasting, such as cirrhosis, cirrhotic sarcopenia, ESLD, hepatic insufficiency, or hepatic encephalopathy.